New guidance from the FDA focuses on human factors in drug products where there is already a reference listed drug (RLD). Enhancing the formulation, consistency, quality and effectiveness of medicines is often seen as continuous improvement – bettering the clinical outcome of how the medicine received by our human bodies. Frequently though, the human factors are overlooked, and so the FDA have sought to not allow this to happen in future abbreviated new drug applications (ANDA’s).
The guidance is intended to assist pharmaceutical organisations who plan to develop and submit an abbreviated new drug application (ANDA) to seek approval of a proposed combination product that includes both a drug constituent part and a delivery device constituent part. This includes pre-filled syringes, auto-injectors, pen injectors, infusion systems, oral dispensers and generic drugs.
The guidance details methods for defining the differences between the new proposed drug delivery combination product and any existing product. This includes the theoretical analysis of the user interfaces and the differences between them, often documented in Threshold Analyses (Labelling comparisons, comparative task analyses and physical comparative assessments). The aim of these threshold analyses is to determine design differences. If the design difference is minor, then further human factors evidence may not be required. If though the design difference affects a critical design attribute, such as the method of administration, then additional human factors evidence would be required. It has to be based upon safety, and evidence of comparable use safety can be demonstrated though risk or clinical evaluation – at least in a theoretical manner. A key question to perhaps ask is whether the safety or clinical profile will change with the new drug product or not?
For minor design differences, a comparative human factors evaluation is only partially sufficient to evaluate and compare the use safety profile of the new drug product against its reference listed drug product. This is because a comparative human factors evaluation will have to be performed in addition to a typical human factors validation evaluation.
In a comparison human factors evaluation, it is vital that the new drug product has an equivalent or better use safety profile than the reference listed drug product – at least in terms of the critical tasks and critical design attributes. Noninferiority (NI) study design is additionally a proposed method of evaluation (rather than a pure equivalence study method) if there is the comparison between a generic drug product and a reference listed drug product. All methods of proving equivalence and noninferiority should be used – including the use of statistics to ensure a trustworthy result can be determined. Statistical methods also mean that sample sizes for use in the testing are subject to a different thinking than typical human factors evaluations. The guidance recommends that the sample size is large enough to demonstrate equivalence and this can mean a significant increase in sample size – which could be over 100 participants if the statistical power range required is high (>75%) as an example. More details can be found in the guidance on the FDA website.
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The staff at THAY Medical